Anxiety Disorders are among the most common mental health disorders, affecting about 40 million American adults age 18 years and older (about 18%) in a given year (Kessler et al. Arch. Gen. Psych 2005). They generally last at least six months and can get worse if not treated. While the cause is not clear, they are believed to have biological, social and psychological components ranging from heredity, personality, life experiences including reactions to stress such as traumatic events, and brain chemistry such as low neurotransmitter levels and problems with amygdala functioning. Anxiety disorders can result in persistent and disabling psychological and physiological symptoms that interfere with the day to day life of an affected individual and include disorders such as acute stress disorder, panic disorder, generalized anxiety disorder, agoraphobia with or without panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, separation anxiety disorder, and post-traumatic stress disorder.
Symptoms of anxiety disorders may vary depending on the disorder, but may include feelings of panic; persistent worry; doubt; dread; fear; uneasiness; uncontrollable, obsessive thoughts; repeated thoughts or flashbacks of traumatic experiences; mood instability; agitation; restlessness; dyspepsia; headaches; dyspnea; nightmares; sleep disturbances; ritualistic behaviors, such as repeated hand washing; insomnia; cold or sweaty hands and/or feet; shortness of breath; palpitations; an inability to be still and calm; intense startle reflex; dry mouth; numbness or tingling in the hands or feet; nausea; muscle tension; and/or dizziness.
Acute stress disorder is a result of a traumatic event in which the person experienced or witnessed an event that involved threatened or actual serious injury or death and responded with intense fear and helplessness. Symptoms include dissociative symptoms such as numbing, detachment, a reduction in awareness of the surroundings, derealization, or depersonalization, re-experiencing of the trauma, avoidance of associated stimuli, and significant anxiety, including irritability, poor concentration, difficulty sleeping, and restlessness. If left untreated, the condition may evolve into Post-traumatic Stress Disorder (PTSD).
Panic Disorder is characterized by sudden attacks of intense fear or anxiety, usually associated with numerous physical symptoms such as heart palpitations, rapid breathing or shortness of breath, blurred vision, dizziness, and racing thoughts. Generalized anxiety disorder is evidenced by general feelings of anxiety such as mild heart palpitations, dizziness, and excessive worry. Agoraphobia is the anxiety of being in places where escape might be difficult or embarrassing or in which help may not be available should a panic attack develop. Phobias result in extreme anxiety and/or fear associated with the object or situation of avoidance. Obsessive compulsive disorders are characterized by persistent, often irrational, and seemingly uncontrollable thoughts and actions which are used to neutralize the obsessions.
PTSD results from experiencing or witnessing a traumatic event that causes intense fear, helplessness or horror. It results in symptoms that fall into three types: re-experiencing the event, emotional numbing and avoidance and hyperarousal. Repetition of these overwhelming emotions can lead to a cascade of biological events including excessive release of epinephrine and norepinephrine which overpowers the autonomic response leading to clamminess, increased heart rate and breathing, increased blood flow to the muscles and decreased blood flow to the visceral organs. It is currently theorized that this response leads to deep imprinting on the locus coeruleus region of the brain and makes it over sensitized to any further threats (real or imaginary). (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) published by the American Psychiatric Association (APA; Washington, D.C., 1994). PTSD, as that term is used herein, also encompasses the 4 categories of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) published by the American Psychiatric Association (APA; Washington, D.C., 2013), which include intrusion (e.g., re-experiencing), avoidance, negative alterations in mood and cognition and alterations in arousal and reactivity. PTSD is also believed to involve the serotonergic and endorphin system. (Holbrook et al, 2010). Experiments have consistently shown a serotonin deficit in “stressed” animals. Through multiple interconnections with the limbic system, serotonin has been found to mediate response to acute and chronic stress, conditioned fear, and flight or fight responses. Further, serotonin also modulates norepinephrine levels thereby leading to indirect effects on stress response through the adrenergic system.
Exposure to traumatic events is common with more than 50% of the US population experiencing one or more traumatic events in their lifetime. (Kessler et al., 1995) However, the rates of PTSD varies according to the population with a lifetime prevalence of approximately 5 to 12% of the population with women having twice the prevalence rate of men (Kessler et al., 1995) and certain segments of the population, such as combat soldiers having rates as high as 25%.
Anxiety disorders are generally treated with a combination of medication and psychotherapy. However, many of the currently prescribed medications merely keep anxiety disorders under control while psychotherapy is attempted, they do not actually treat the disorder. In the case of some disorders, very few medications have been approved. For example, only two medications, sertraline and paroxetine, have been approved by the FDA for treatment of Post-traumatic Stress Disorder. The medications currently used to treat anxiety disorders have unwanted characteristics and side effects including drug interactions, cardiovascular side effects, gastrointestinal side effects, sexual side effects, suicidal ideation and slow onset of action. Even with treatment, residual symptoms and poor functioning continue to be a problem for those suffering from or at risk for anxiety disorders. There is therefore a need in the art for the discovery of additional treatments for anxiety disorders including PTSD.